11,12-Diacetyl-carnosol Protects SH-SY5Y Cells from Hydrogen Peroxide Damage through the Nrf2/HO-1 Pathway

Background. Oxidative stress-induced neurotoxicity plays a key role in Alzheimer’s disease (AD). 11,12-Diacetyl-carnosol (NO.20), an acetylated derivative of carnosol extracted from rosemary, displays a high antioxidative effect in vitro. Purpose. We investigated the neuroprotective effect of NO.20...

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Published in:	Evidence-based complementary and alternative medicine 2022, Vol.2022, p.4376812-12
Main Authors:	Luo, Qingyi, Hu, Weiyan, Yu, Haofei, Zhang, Rongping, Chen, Xinglong
Format:	Article
Language:	eng
Subjects:	Alzheimer's disease Alzheimers disease Antioxidants Apoptosis Bax protein Bcl-2 protein Biotechnology industry Caspase-3 Cell culture Cytochrome Cytochrome c Cytotoxicity Diacetyl Drug dosages Glutathione Heme Heme oxygenase (decyclizing) Hydrogen peroxide Medical research Membrane potential Mitochondria Neurodegenerative diseases Neuroprotection Neurotoxicity NRF2 protein Nuclear transport Oxidative stress Oxygenase Proteins Reactive oxygen species siRNA
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Summary:	Background. Oxidative stress-induced neurotoxicity plays a key role in Alzheimer’s disease (AD). 11,12-Diacetyl-carnosol (NO.20), an acetylated derivative of carnosol extracted from rosemary, displays a high antioxidative effect in vitro. Purpose. We investigated the neuroprotective effect of NO.20 on H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and its possible mechanism. Results. We found that NO.20 pretreatment (1 μM for 1 h) had cytoprotective effects and weakened H2O2-induced damage in SH-SY5Y cells by reducing viability loss, apoptotic rate, and reactive oxygen species production. In addition, NO.20 inhibited H2O2-induced mitochondrial dysfunctions: it alleviated mitochondrial membrane potential loss and cytochrome c release, decreased the Bax/Bcl-2 ratio, and reduced caspase-3 expression. NO.20 also downregulated malondialdehyde and upregulated glutathione. Furthermore, NO.20 pretreatment caused the nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), increasing heme oxygenase-1 (HO-1) expression in SH-SY5Y cells. Notably, we found that silencing Nrf2 using small interfering RNA (siRNA) suppressed the NO.20-induced HO-1 expression and abolished the neuroprotective effect of NO.20. Conclusion. These results demonstrate that NO.20 protects SH-SY5Y cells from H2O2-induced neurotoxicity by activating the Nrf2/HO-1 pathway. Thus, the neuroprotective and antioxidative stress effects of NO.20 may make it a promising neuroprotective compound for AD treatment.
ISSN:	1741-427X 1741-4288